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Anwarul Haq, MD, MRCP(UK) Neurologist
BUMC
It is a relentlessly progressive disease of the Motor System Commonly known as Lou Gehrig’s Disease Called Motor Neuron Disease in Britain A relatively uncommon disorder Incidence 1.8/100,000 population Prevalence of 2-7/100, 000 population
The ‘iron horse’
History First described by Charcot
in 1869
The science of ALS, however, remained largely descriptive
In 1990 World Federation of Neurology met in El Escorial, Spain and published the diagnostic criteria for ALS
The EE criteria was considered too restrictive and was relaxed in 1998
The first breakthrough came in 1991
Teepu Siddique et al, at Northwestern University Chicago, identified the 1st genetic mutation causing ALS in some families
Superoxide dismutase gene on chromosome 21
This led to the development of animal models of ALS and the ability to rationally develop and test drugs for ALS
In 1994 Riluzole was reported to prolong survival in ALS (Bensimon et al)
Multiple other genetic mutations have since been identified in familial ALS
How is the Nervous System organized?
What is in the motor system?
Lower motor neuron (LMN) signs: Weakness, muscle wasting, hyporeflexia, muscle cramps,
fasciculations, weakness
Upper motor neuron (UMN) signs: Spasticity, hyper-reflexia, weakness
Epidemiology Incidence 1.8/100,000 population Prevalence of 2-7/100, 000 population In the United States, about 7000 new cases of ALS are
diagnosed each year 90% of cases are sporadic 10% are familial (FALS); most commonly autosomal
dominant Male:Female – 1.4: 1 Average age at onset is ~ 60 years Can start in teens or >75yrs
Glutamate excitotoxicity Free radical injury Neurofilament and Microtubule dysfunction Ubiquilin2 (which is involved in recycling damaged and
misformed proteins in key nerve cells). In people with ALS, ubiquilin2 does not do this effectively, leading to an accumulation of the damaged proteins and ubiquilin2 in critical nerve cells in the spinal cord and brain (Nature 2011)
Patients present with a combination of upper and lower motor neuron signs
Clinical patterns at presentation Progressive bulbar palsy Progressive Muscular Atrophy Primary lateral sclerosis ALS (UMN + LMN)
These patterns then progressively merge to develop full blown ALS picture (UMN + LMN)
Tongue atrophy
Leg wasting
Hand atrophy
El Escorial criteria
Prognosis Mean survival from onset is 23-43 months 5-yr. survival rate of 22% 10-yr. survival rate of 9.4% Poor prognostic factors:
Age >65 yr Rapid disease progression Dyspnea at onset Rapid decline in pulmonary function
Can any tests help in diagnosis? There is no blood marker of S-ALS Diagnosis depends on the clinical picture EMG can be helpful by showing characteristic findings:
fibrillations, fasciculations, reinnervation motor units Blood tests and imaging can help rule out other diseases
Multidisciplinary Approach
Neurologist Clinical/research nurse Dietician Speech/swallowing
therapist Family/caregivers Psychologists
Physical therapist Occupational therapist Social worker GI physician Support organizations Homehealth/hospice Pulmonologist
Phramacotherapy - specific Riluzole was approved in 1996 It acts as an antiglutamate agent Median prolongation of survival of 2 months
Phramacotherapy - symptomatic Fatigue: pyridostigmine, SSRIs, Amantadine Spasticity: Baclofen, Tizanidine Cramps: Quinine, Clonazepam Psedobulbar affect: Dextromethorphan/Quinidine, SSRIs, Depressions: SSRIs, TCAs,
Speech and Communication Speech therapists to be involved early Introduce energy conserving skills Introduce non-verbal techniques Introduce assistive and augmentative devices
Respiratory care Goals and limitations of any intervention should be
discussed in detail Non-invasive Positive Pressure Ventilation is used Generally offered when FVC <50%, patient is short of
breath or when symptomatic hypercapnia occurs
Thank you
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